high intravenous doses during combination chemotherapeutic regimens (see section 4.8).
Delayed progressive ascending paralysis resulting in death has been reported in children with AML following intravenous cytarabine at conventional doses in combination with other drugs.
Cytarabine has been shown to be mutagenic and carcinogenic in animals. The possibility of a similar effect should be borne in mind when designing the long-term management of the patient.
Cytarabine should only be used under the constant supervision by physicians experienced in therapy with cytotoxic agents. Hyperuricemia secondary to rapid lysis of neoplastic cells may occur in patients receiving cytarabine; serum uric acid concentrations should be monitored. The physician should be prepared to use such supportive and pharmacological measures as may be necessary to control this problem.
Periodic determinations of renal and hepatic functions and bone marrow should also be performed and the drug should be used with caution in patients with impaired hepatic function.
However, dosage reduction does not appear to be necessary in patients with impaired renal function. The human liver apparently detoxifies a substantial fraction of the administered dose. The drug should be used with caution and at a reduced dose when liver function is poor. Frequent platelet and leucocyte counts are mandatory.
Therapy should be suspended or modified when drug-induced bone marrow depression results in a platelet count of less than 50,000 or a polymorph nuclear count of under 1000 per mm3. Counts may continue to fall after the therapy has been discontinued and may reach lowest values after five to seven days. Therapy may be restarted when the bone marrow appears to be recovering on successive bone marrow studies. Therapy should not wait until the normal blood values are obtained to be re-initiated. If treatment is not resumed before blood values return to normal, the disease can get out of control.
When intravenous doses are given quickly, patients may become nauseated and may vomit for several hours afterwards. The problem tends to be less severe when infused.
Abdominal tenderness (peritonitis) and guaiac positive colitis, with concurrent neutropenia and thrombocytopenia, have been reported in patients treated with conventional doses of cytarabine in combination with other drugs. Patients have responded to non-operative medical management.
Concurrent granulocyte-transfusion should be avoided as severe respiratory insufficiency has been reported.
Immunosuppressant effects/Increased susceptibility to infections
Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including cytarabine, may result in serious or fatal infections. Vaccination with a live vaccine should be avoided in patients receiving cytarabine. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.
High dose therapy
Peripheral motor and sensory neuropathies after consolidation with high doses of cytarabine, daunorubicin, and asparaginase have occurred in adult patients with acute non lymphocytic leukaemia.
Patients treated with high doses of cytarabine should be observed for neuropathy since dose adjustments may be needed to avoid irreversible neurologic disorders.
Severe and sometimes fatal pulmonary toxicity, adult respiratory distress syndrome, and pulmonary oedema have occurred follow |
